Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain

Molecular Psychiatry

Volumn 18, Issue 8, 2013, Pages 882-888

  Steele, J W ^a,b   Ju, S ^c   Lachenmayer, M L ^a,d   Liken, J ^c   Stock, A ^a   Kim, S H ^a   Delgado, L M ^e   Alfaro, I E ^f   Bernales, S ^f,g   Verdile, G ^h   Bharadwaj, P ^h   Gupta, V ^h   Barr, R ^h   Friss, A ^a   Dolios, G ^a   Wang, R ^a   Ringe, D ^c   Protter, A A ^g   Martins, R N ^h,i,j   Ehrlich, M E ^a   Yue, Z ^a   Petsko, G A ^a,k   Gandy, S ^a,l   more..

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b ROCKEFELLER UNIVERSITY   (United States)

^c BRANDEIS UNIVERSITY   (United States)

^d UNIVERSITY OF BONN   (Germany)

^e UNIVERSIDAD ANDRÉS BELLO   (Chile)

^f Fundacion Ciencia para la Vida   (Chile)

^g Medivation Inc   (United States)

^h EDITH COWAN UNIVERSITY   (Australia)

ⁱ UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^j HOLLYWOOD PRIVATE HOSPITAL   (Australia)

^k WEILL CORNELL MEDICAL COLLEGE   (United States)

^l VETERANS AFFAIRS MEDICAL CENTER   (United States)

more..

Author keywords

synuclein; autophagy; proteotoxicity; therapeutics

Indexed keywords

ALPHA SYNUCLEIN; DIMEBON; FUSED IN SARCOMA PROTEIN; HUNTINGTIN; POLYGLUTAMINE; TAR DNA BINDING PROTEIN;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOPHAGY; CELL STIMULATION; CELL VIABILITY; CLEARANCE; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFECT; HUMAN; HUMAN CELL; LONG TERM CARE; MALE; MOUSE; NERVE CELL; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; SACCHAROMYCES CEREVISIAE; WILD TYPE;

ALPHA-SYNUCLEIN; AMYLOID BETA-PEPTIDES; ANIMALS; AUTOPHAGY; BRAIN; CELL DEATH; CELLS, CULTURED; HUMANS; INDOLES; MALE; MICE; NEUROPROTECTIVE AGENTS; PEPTIDE FRAGMENTS; SACCHAROMYCES CEREVISIAE;

EID: 84881158430     PISSN: 13594184     EISSN: 14765578     Source Type: Journal    
DOI: 10.1038/mp.2012.115     Document Type: Article

References (35)

1. Lermontova NN, Lukoyanov NV, Serkova TP, Lukoyanova EA, Bachurin SO. Dimebon improves learning in animals with experimental Alzheimer's disease. Bull Exp Biol Med 2000; 129: 544-546
2. Grigorev VV, Dranyi OA, Bachurin SO. Comparative study of action mechanisms of dimebon and memantine on AMPA-And NMDA-subtypes glutamate receptors in rat cerebral neurons. Bull Exp Biol Med 2003; 136: 474-477
3. Giorgetti M, Gibbons JA, Bernales S, Alfaro IE, Drieu La Rochelle C, Cremers T et al. Cognition-enhancing properties of dimebon in a rat novel object recognition task are unlikely to be associated with acetylcholinesterase inhibition or N-methyl-Daspartate receptor antagonism. J Pharmacol Exp Ther 2010; 333: 748-757
4. Wang J, Ferruzzi MG, Varghese M, Qian X, Cheng A, Xie M et al. Preclinical study of dimebon on beta-Amyloid-mediated neuropathology in Alzheimer's disease. Mol Neurodegener 2011; 6: 7
5. Bachurin S, Bukatina E, Lermontova N, Tkachenko S, Afanasiev A, Grigoriev V et al. Antihistamine agent dimebon as a novel neuroprotector and a cognition enhancer. Ann NY Acad Sci 2001; 939: 425-435
6. Wu J, Li Q, Bezprozvanny I. Evaluation of dimebon in cellular model of Huntington's disease. Mol Neurodegener 2008; 3: 15
7. Pieper AA, Xie S, Capota E, Estill SJ, Zhong J, Long JM et al. Discovery of a prone urogenic, neuroprotective chemical. Cell 2010; 142: 39-51
8. Doody RS, Gavrilova SI, Sano M, Thomas RG, Aisen PS, Bachurin SO et al. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-To-moderate Alzheimer's disease: A randomised, double-blind, placebo-controlled study. Lancet 2008; 372: 207-215
9. Kieburtz K, McDermott MP, Voss TS, Corey-Bloom J, Deuel LM, Dorsey ER et al. A randomized, placebo-controlled trial of latrepirdine in Huntington disease. Arch Neurol 2010; 67: 154-160
10. Bharadwaj P, Verdile G, Barr RK, Gupta V, Steele JW, Lachenmayer ML et al. Latrepirdine (Dimebont) enhances autophagy and reduces intracellular GFPAb42 levels in yeast. J Alzheimer's Disease (in press
11. Bachurin SO, Shelkovnikova TA, Ustyugov AA, Peters O, Khritankova I, Afanasieva MA et al. Dimebon slows progression of proteinopathy in gamma-synuclein transgenic mice. Neurotox Res 2012; 22: 33-42
12. Walsh DM, Selkoe DJ. Oligomers on the brain: The emerging role of soluble protein aggregates in neurodegeneration. Protein Peptide Lett 2004; 11: 213-228
13. Broe M, Shepherd CE, Mann DM, Milward EA, Gai WP, Thiel E et al. Insoluble alphasynuclein in Alzheimer's disease without Lewy body formation. Neurotox Res 2005; 7: 69-76
14. Uchikado H, Lin WL, DeLucia MW, Dickson DW. Alzheimer disease with amygdala Lewy bodies: A distinct form of alpha-synucleinopathy. J Neuropathol Exp Neurol 2006; 65: 685-697
15. Wirths O, Bayer TA. Alpha-synuclein, Abeta and Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 103-108
16. Bartels T, Choi JG, Selkoe DJ. Alpha-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 2011; 477: 107-110
17. Tian Y, Bustos V, Flajolet M, Greengard P. A small-molecule enhancer of autophagy decreases levels of Abeta and APP-CTF via Atg5-dependent autophagy pathway. FASEB J 2011; 25: 1934-1942
18. Sarkar S, Perlstein EO, Imarisio S, Pineau S, Cordenier A, Maglathlin RL et al. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat Chem Biol 2007; 3: 331-338
19. Steele JW, Lachenmayer ML, Ju S, Stock A et al. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model. submitted manuscript
20. Steele JW, Kim SH, Cirrito JR, Verges DK, Restivo JL, Westaway D et al. Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic, elevates extracellular amyloid-beta levels in vitro and in vivo. Mol Neurodegener 2009; 4: 51
21. Klionsky DJ. Monitoring autophagy in yeast: The Pho8Delta60 assay. Methods Mol Biol 2007; 390: 363-371
22. Vekrellis K, Xilouri M, Emmanouilidou E, Stefanis L. Inducible over-expression of wild type alpha-synuclein in human neuronal cells leads to caspase-dependent non-Apoptotic death. J Neurochem 2009; 109: 1348-1362
23. Outeiro TF, Lindquist S. Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science 2003; 302: 1772-1775
24. Tanaka M, Chien P, Yonekura K, Weissman JS. Mechanism of cross-species prion transmission: An infectious conformation compatible with two highly divergent yeast prion proteins. Cell 2005; 121: 49-62
25. Noda T, Ohsumi Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 1998; 273: 3963-3966
26. Yue Z, Friedman L, Komatsu M, Tanaka K. The cellular pathways of neuronal autophagy and their implication in neurodegenerative diseases. Biochim Biophys Acta 2009; 1793: 1496-1507
27. Knauer MF, Soreghan B, Burdick D, Kosmoski J, Glabe CG. Intracellular accumulation and resistance to degradation of the Alzheimer amyloid A4/beta protein. Proc Natl Acad Sci USA 1992; 89: 7437-7441
28. Ebrahimi-Fakhari D, Cantuti-Castelvetri I, Fan Z, Rockenstein E, Masliah E, Hyman BT et al. Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of alpha-synuclein. J Neurosci 2011; 31: 14508-14520
29. Friedman LG, Lachenmayer ML, Wang J, He L, Poulose SM, Komatsu M et al. Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of a-synuclein and LRRK2 in the brain. J Neurosci 2012; 32: 7585-7593
30. Miller G. Pharmacology. The puzzling rise and fall of a dark-horse Alzheimer's drug. Science 2010; 327: 1309
31. Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ, Bhullar B et al. Alphasynuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 2006; 313: 324-328
32. Ju S, Tardiff DF, Han H, Divya K, Zhong Q, Maquat LE et al. A yeast model of FUS/TLS-dependent cytotoxicity. PLoS Biol 2011; 9: E1001052
33. Johnson BS, McCaffery JM, Lindquist S, Gitler AD. A yeast TDP-43 proteinopathy model: Exploring the molecular determinants of TDP-43 aggregation and cellular toxicity. Proc Natl Acad Sci USA 2008; 105: 6439-6444
34. Willingham S, Outeiro TF, DeVit MJ, Lindquist SL, Muchowski PJ. Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein. Science 2003; 302: 1769-1772
35. He C, Song H, Yorimitsu T, Monastyrska I, Yen WL, Legakis JE et al. Recruitment of Atg9 to the preautophagosomal structure by Atg11 is essential for selective autophagy in budding yeast. J Cell Biol 2006; 175: 925-935